During the previous funding cycle of this project (R01 MH073402) we identified distinct subtypes of repetitive behavior validated by the presence of subtype-specific clinical correlates. The potential impact of this finding is that these distinct repetitive behavior subtypes could be leveraged to help parse the biological, behavioral, and treatment-response heterogeneity that heretofore has constrained research on the etiology and treatment of autism. This idea is the focus of our next round of studies in this systematic program of research on repetitive behaviors: By focusing on specific subtypes of repetitive behaviors, can we identify unique pathophysiologic factors that could be used to guide the development of novel treatment strategies? Our focus in this application is on one of these distinct subtypes of repetitive behavior - unusual and intense interests, preoccupations, and attachments - that has received virtually no attention in autism. In recent studies we have found that these so-called "Circumscribed Interests" (CI) appear to impart significant added impairment in autism over and above other core deficits. Clinically, CI seem to be associated with strong positive affect and anticipatory motivation in contrast to repetitive behaviors in other disorders such as obsessive compulsive disorder (OCD) that seem to be associated with negative affect and anxiety-reduction (e.g. rituals, compulsions, insistence on sameness). The heightened interest and restricted focus that are characteristic of CI suggest that the functioning of neural circuitry that mediate reward processing may be altered in persons with autism. Consistent with this, we hypothesize that the development of CI in autism is mediated by an underlying cognitive-affective reward system that is "biased" away from social information and towards nonsocial information and thus that a unique cognitive-attentional phenotype may characterize CI. The goals of the proposed continuation of this project are to elucidate the clinical significance of CI in autism and to identify cognitive and neurobiological markers of this subtype. We propose to compare children (ages 12 - 18 years) with low-functioning (n = 40) and high-functioning autism (n = 40) to individuals with obsessive-compulsive disorder (n = 40), developmental delay (n=40) and typically developing controls (n = 40) on (a) a standardized assessment battery for measuring CI and the other varieties of repetitive behavior (Aim 1);(b) a passive visual exploration, eye-tracking task that measures differential attention to CI and non-CI images (Aim 2);and (c) to compare the HFA and TYP samples on two fMRI tasks comparing brain activation to CI versus non-CI images under conditions of reward anticipation and target detection (Aim 3). PUBLIC HEALTH RELEVANCE: Autism is a devastating neurodevelopmental disorder that is characterized by restricted repetitive behaviors. We propose to examine which types of repetitive behaviors are clinically significant for persons with autism. Answering this question would refine diagnostic practice, would focus the search for specific genetic, neurobiologic, and cognitive mechanisms of autism, and would ultimately direct the development of novel forms of treatment for autism.